The objective of this research is to study the mechanisms whereby experimental alterations in motor nerve function produce muscle disease. These are continuing studies of an experimental model of myopathy which is believed to be acetylcholine mediated. The models are produced by chronic inhibition of cholinesterase with paraoxon and by enhancing the release of acetylcholine with quanidine. Included are: 1) further studies on the selective vulnerability of tonic muscle to necrosis; 2) clarification of the earliest events, physiological and morphological, related to endplate necrosis; 3) studies on the mechanisms of adaptation to chronic cholinesterase inhibition; and 4) new studies to determine how alterations in axoplasmic flow and the electrochemical events of neurotransmission affect the experimental myopathies. The methods employed are: 1) histochemistry, 2) electrophysiology 3) biochemistry and 4) electron microscopy.